Hydrophilic molecules such as nucleic acids or water-soluble drugs are often carried by lipid vesicles providing a protective environment so that said molecules can cross cell membranes and enter target cells. Lipid vesicles are substantially spherical structures made of materials having a high amphiphilic lipid content. Lipid vesicles are usually called liposomes, if the lipid molecules are orientated in a lipid bilayer around an aqueous cave. Hydrophilic molecules but also hydrophobic molecules as well as amphiphilic molecules can be carried by liposomes. In particular, hydrophilic molecules can be carried by liposomes being comprised in the aqueous internal space of the liposomes, hydrophobic molecules can be carried by liposomes being comprised in the lipid bilayer of the liposomes and amphiphilic molecules can be carried by liposomes being comprised at the interface between lipid bilayer and aqueous internal space of the liposomes. Liposomes can be distinguished by their form and size and can be classified, for example, in multilamellar vesicles (MLV), large unilamellar vesicles (LUV), small unilamellar vesicles (SUV) or in other forms.
In the last decades, a wide range of liposome formulations have been investigated for use in medical applications, cosmetics or food industry. The first most prominent liposome-based products are the cancer drugs Doxil (Sequus) and DaunoXome (Gilead, Nexstar), which have been approved by the US Food and Drug Administration (FDA) in the 1990s (Wagner, A., Vorauer-Uhl, K., (2011), Journal of Drug Delivery, 2011:591325). Recent investigations resulted in the generation of new classes of liposomes such as dendrosomes (Sarbolouki, M. N., Sadeghizadeh, M., Yaghoobi, M. M., Karami, A., Lohrasbi, T. (2000), Journal of Chemical Technology and Biotechnology, 75, 919-922) or cationic liposomes (Audouy, S., Hoekstra, D. (2001), Molecular Membrane Biology, 18, 129-143). Cationic liposomes are structures that are made of positively charged lipids and are increasingly being researched for use in gene therapy due to their favourable interactions with negatively charged DNA and cell membranes. Recently, cationic liposomes have been provided not only for carrying DNA molecules but also for carrying RNA molecules or other therapeutically active compounds.
Disadvantages of current liposomes are that they need to be tailored for a given type of compound. For example, lipophilic, hydrophilic or polymeric compounds need different lipidic carriers to obtain suitable payload and targeting efficacy. One problem with water soluble compounds is the susceptibility to leakage, for example on binding to proteins, peptides, polynucleic acids or polymers in general. Thus, there is a need of improved formulations of particles for the delivery of therapeutically active compounds.
As mentioned above, lipid particles, such as liposomes, have usually therapeutic active compounds encapsulated in their interior. The present inventors surprisingly found that with particles having water-soluble compounds encapsulated in their lipid vesicular core RNA can be bound thereon, maintaining the vesicular organization, and maintaining, partially or completely the encapsulated compound. The RNA decoration does not lead to loss of the encapsulated therapeutically active compound. It is known that RNA molecules are easily degraded in body fluids after systemic administration by ribonucleases. The present inventors surprisingly found that the RNA on the RNA decorated particles is stable and does not form aggregates.